Wang Tso-Jen, Huang San-Yuan, Lin Wei-Wen, Lo Hsin-Yi, Wu Pei-Lin, Wang Yu-Shan, Wu Yi-Syuan, Ko Huei-Chen, Shih Jean-Chen, Lu Ru-Band
Graduate Institute of Medical Sciences, National Defense Medical Center, Taiwan, ROC; Tsaotun Psychiatric Center, Department of Health, Nantou, Taiwan, ROC.
Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jan 30;31(1):108-14. doi: 10.1016/j.pnpbp.2006.08.010. Epub 2006 Sep 27.
Both monoamine oxidase A (MAOA) and dopamine D(2) receptor (DRD2) genes have been considered as candidate genes for antisocial personality disorder with alcoholism (Antisocial ALC) [Parsian, A., 1999. Sequence analysis of exon 8 of MAO-A gene in alcoholics with antisocial personality and normal controls. Genomics. 45, 290-295.; Samochowiec, J., Lesch, K.P., Rottmann, M., Smolka, M., Syagailo, Y.V., Okladnova, O., Rommelspacher, H., Winterer, G., Schmidt, L.G., Sander, T., 1999. Association of a regulatory polymorphism in the promoter region of the monoamine oxidase A gene with antisocial alcoholism. Psychiatry. Res. 86, 67-72.; Schmidt, L.vG., Sander, T., Kuhn, S., Smolka, M., Rommelspacher, H., Samochowiec, J., Lesch, K.P., 2000. Different allele distribution of a regulatory MAO-A gene promotor polymorphism in antisocial and anxious-depressive alcoholics. J. Neural .Transm. 107, 681-689.]. However, the association between alcoholism and MAOA or DRD2 gene has not been universally accepted [Lee, J.F., Lu, R.B., Ko, H.C., Chang, F.M., Yin, S.J., Pakstis, A.J., Kidd, K.K., 1999. No association between DRD(2) locus and alcoholism after controlling the ADH and ALDH genotypes in Chinese Han population. Alcohol. Clin. Exp. Res. 23, 592-599.; Lu, R.B., Lin, W.W., Lee, J.F., Ko, H.C., Shih, J.C., 2003. Neither antisocial personality disorder nor antisocial alcoholism association with MAOA gene among Han Chinese males in Taiwan. Alcohol. Clin. Exp. Res. 27, 889-893.]. Since dopamine is metabolized to 3,4-dihydroxyphenyl-acetaldehyde (DOPAL) via monoamine oxidase (MAO) [Westerink, B.H., de Vries, J.B., 1985. On the origin of dopamine and its metabolite in predominantly noradrenergic innervated brain areas. Brain. Res. 330, 164-166.], the interaction between MAOA and DRD2 genes might be related to Antisocial ALC. The present study aimed to determine whether Antisocial ALC might be associated with the possible interactions of DRD2 gene with MAOA gene. Of the 231 Han Chinese subjects who were recruited for the study, 73 participants were diagnosed with Antisocial ALC and 158 subjects were diagnosed with antisocial personality disorder without alcoholism (Antisocial Non-ALC). The DRD2 TaqI A and MAOA-uVNTR (variable number of tandem repeat located upstream) polymorphisms were not found to be associated with Antisocial ALC. However, an association between DRD2 TaqI A polymorphisms and Antisocial ALC was shown only after stratification for the MAOA-uVNTR 4-repeat polymorphism. Additionally, after multiple logistic regressions, we found that, under stratification of MAOA-uVNTR 4-repeat polymorphism and in comparison with the DRD2 A1/A1 genotype as a reference group, the DRD2 A1/A2 genotype has a possible protective effect against alcoholism in individuals with antisocial personality disorder (ASPD). We concluded that the possible interactions between MAOA-uVNTR polymorphism and DRD2 TaqI A polymorphism might be related to Antisocial ALC among Han Chinese men in Taiwan.
单胺氧化酶A（MAOA）基因和多巴胺D2受体（DRD2）基因都被视为伴有酒精中毒的反社会人格障碍（反社会型酒精中毒）的候选基因[帕西安，A.，1999年。反社会人格障碍酒精依赖者与正常对照者MAO - A基因第8外显子序列分析。基因组学。45，290 - 295页；萨莫乔维茨，J.，莱施，K.P.，罗特曼，M.，斯莫尔卡，M.，西亚伊洛，Y.V.，奥克拉德诺娃，O.，罗梅尔施帕赫，H.，温特勒，G.，施密特，L.G.，桑德，T.，1999年。单胺氧化酶A基因启动子区域调控多态性与反社会型酒精中毒的关联。精神病学研究。86，67 - 72页；施密特，L.vG.，桑德，T.，库恩，S.，斯莫尔卡，M.，罗梅尔施帕赫，H.，萨莫乔维茨，J.，莱施，K.P.，2000年。反社会型和焦虑抑郁型酒精依赖者中调控MAO - A基因启动子多态性的不同等位基因分布。神经传递杂志。107，681 - 689页]。然而，酒精中毒与MAOA或DRD2基因之间的关联尚未得到普遍认可[李，J.F.，卢，R.B.，柯，H.C.，张，F.M.，尹，S.J.，帕克斯蒂斯，A.J.，基德，K.K.，1999年。在中国汉族人群中控制ADH和ALDH基因型后DRD(2)位点与酒精中毒无关联。酒精临床与实验研究。23，592 - 599页；卢，R.B.，林，W.W.，李，J.F.，柯，H.C.，施，J.C.，2003年。台湾汉族男性中反社会人格障碍或反社会型酒精中毒与MAOA基因无关联。酒精临床与实验研究。27，889 - 893页]。由于多巴胺通过单胺氧化酶（MAO）代谢为3,4 - 二羟基苯乙醛（DOPAL）[韦斯特林克，B.H.，德弗里斯，J.B.，1985年。多巴胺及其代谢产物在主要由去甲肾上腺素能神经支配的脑区的起源。脑研究。330，164 - 166页]，MAOA和DRD2基因之间的相互作用可能与反社会型酒精中毒有关。本研究旨在确定反社会型酒精中毒是否可能与DRD2基因与MAOA基因的可能相互作用有关。在招募的231名汉族受试者中，73名参与者被诊断为反社会型酒精中毒，158名受试者被诊断为无酒精中毒的反社会人格障碍（反社会非酒精中毒）。未发现DRD2 TaqI A和MAOA - uVNTR（位于上游的可变串联重复序列）多态性与反社会型酒精中毒相关。然而，仅在根据MAOA - uVNTR 4重复多态性进行分层后，才显示出DRD2 TaqI A多态性与反社会型酒精中毒之间的关联。此外，经过多元逻辑回归分析，我们发现，在MAOA - uVNTR 4重复多态性分层的情况下，与以DRD2 A1/A1基因型为参照组相比，DRD2 A1/A2基因型对患有反社会人格障碍（ASPD）的个体的酒精中毒可能具有保护作用。我们得出结论，MAOA - uVNTR多态性与DRD2 TaqI A多态性之间的可能相互作用可能与台湾汉族男性的反社会型酒精中毒有关。
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